FDA-approved controlled-delivery polymer wafer— Gliadel® (Guilford Pharmaceutical Corp, Baltimore, Md.), is the combination of a copolyanhydride matrix consisting of CPP and sebacic acid (in 20 to 80 molar ratios,) in which the anticancer agent is physically admixed (W. Dang et al. J. Contr. Rel. (1996) 42:83-92). Hydrolytic degradation products of Gliadel® wafer (in addition to the anticancer agent) are ultimately the starting di-acids: sebacic acid and CPP. Clinical investigations of Gliadel implants in rabbit brains have shown limited toxicity, initial activity and fast excretion of decomposition products—the free acids (A. J. Domb et al. Biomaterials. (1995) 16:1069-1072).
More recently CPP was disclosed as a monomer useful in preparation of bioabsorbable stents for vascular applications by “Advanced Cardiovascular Systems, Inc”, in patent WO 03/080147 A1, 2003 and polymer particles in co-pending provisional application Ser. No. 60/684,670, filed May 25, 2005.
Another aromatic biodegradable di-acid monomer based on trans-4-hydroxycinnamic acid has been recently described. The monomer with general name 4,4′-(alkanedioyldioxy)dicinnamic acid inherently contains two hydrolytically labile ester groups, and is expected to undergo specific (enzymatic) and nonspecific (chemical) hydrolysis (M Nagata, Y. Sato. Polymer. (2004) 45:87-93). The biodegradable polymers containing unsaturated groups have potential for various applications. For example, unsaturated groups can be converted into other functional groups such as epoxy or alcohol— useful for further modifications. Their crosslinking could enhance thermal and mechanical properties of polymer. Cinnamate is known to undergo reversible [2+2] cycloaddition on UV irradiation at wavelengths over 290 nm, without presence of photoinitiator, which makes the polymer self-photo-crosslinkable (Y. Nakayama, T. Matsuda. J. Polym. Sci. Part A: Polym. Chem. (1992) 30:2451-2457). In addition, the cinnamoyl group is metabolized in the body and has been proven to be non-toxic (Citations in paper of M Nagata, Y. Sato. Polymer. (2004) 45:87-93).
Recent research has also shown that hydrogel-type materials can be used to shepherd various medications through the stomach and into the more alkaline intestine. Hydrogels are cross-linked, hydrophilic, three-dimensional polymer networks that are highly permeable to various drug compounds, can withstand acidic environments, and can be tailored to “swell” and thereby release entrapped molecules through their weblike surfaces. Depending on the chemical composition of the gel, different internal and external stimuli (e.g., changes in pH, application of a magnetic or electric field, variations in temperature, and ultrasound irradiation) may be used to trigger the swelling effect. Once triggered, however, the rate of entrapped drug release is determined solely by the cross-linking ratio of the polymer network.
Chemists, biochemists, and chemical engineers are all looking beyond traditional polymer networks to find innovative drug transport systems. Thus, there is still a need in the art for new and better polymer particle delivery compositions for controlled delivery of a variety of different types of bioactive agents.